New York, Dec 17: Antiretroviral drugs have been life-changing therapies for HIV patients, but they can have significant side effects including neuronal degeneration, which can be manifested as forgetfulness, confusion and behavioural and motor changes, says a study.
Certain protease inhibitors, among the most effective HIV drugs, lead to the production of the peptide beta amyloid, often associated with Alzheimer's disease, the study found.
"Protease inhibitors are very effective antiviral therapies, but they do have inherent toxicities," said senior author on the study Kelly Jordan-Sciutto, Professor at University of Pennsylvania School of Dental Medicine in the US.
The drugs prompt an increase in levels of the enzyme that cleaves the amyloid precursor protein, APP, to produce beta amyloid, which is responsible for the damage to neurons.
Notably, inhibiting that enzyme, called BACE1, protected human and rodent brain cells from harm, suggesting that targetting this mechanism with a new drug could minimise damage to neurons in patients on antiretroviral therapies.
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"Our findings may cause us to rethink how we're using these drugs and even consider developing an adjunctive therapy to reduce some of these negative effects," Jordan-Sciutto noted.
To determine whether and how neuronal damage arises from drug treatment and to ascertain the enzyme BACE1's role, the team investigated the effects of protease inhibitors in two animal models, then probed the mechanism of action in cells in culture.
The findings appeared in the American Journal of Pathology.